Influenza is a highly contagious acute respiratory illness that affects all age groups and causes about 36,000 deaths and over 226,000 hospitalizations per year in the United States alone. Classified (as types A, B, and C), according to antigenic differences in their nucleoprotein and matrix protein, the influenza viruses are enveloped, negative-stranded RNA viruses. The many subtypes of influenza A virus differ in their two surface glycoproteins, hemagglutinin (“HA”) and neuraminidase (“NA”), which are the main targets of the protective immune response, and are labeled according to the type of hemagglutinin (denoted with an H number) and neuraminidase (denoted with an N number). HA and NA vary continuously as a result of antigenic drift and antigenic shift. Sixteen H subtypes (or “serotypes”) and nine N subtypes are known.
Hepatitis B is an infectious illness caused by hepatitis B virus (HBV). About a quarter of the world's population, more than 2 billion people, have been infected with the hepatitis B virus. The acute illness causes liver inflammation, vomiting, jaundice and rarely, death. Chronic hepatitis B may eventually cause liver cirrhosis and liver cancer—a fatal disease with very poor response to current chemotherapy. The hepatitis B virus has a circular genome composed of partially double-stranded DNA and, similar to retroviruses, replicates through an RNA intermediate by reverse transcription. Although replication takes place in the liver, the virus spreads to the blood where virus-specific proteins and their corresponding antibodies are found in infected people.
Cancer is characterized by the uncontrolled growth and spread of abnormal cells. Because tumor cells are derived from normal cells, the host immune system does not recognize tumor cell antigens as foreign. Further, some tumor cells have developed ways to escape the host immune defense system, by eliminating antigens or reducing the number of receptors on the surface of the cell.
Melanoma is a malignant skin cancer that originates in melanocytes. If detected and treated early, it is nearly 100 percent curable. Without early treatment the cancer can advance, spread and be fatal. Melanoma is the skin cancer that causes the most deaths. Superficial spreading melanoma is the most common type of melanoma, especially among young people. This melanoma affects the top layer of the skin for a fairly long time before penetrating more deeply. Lentigo maligna is found most often in the elderly who are chronically exposed to the sun. Acral lentiginous melanoma also spreads superficially before penetrating more deeply and is the most common melanoma in African-Americans and Asians, and the least common among Caucasians. Nodular melanoma is usually invasive at the time it is first diagnosed and is the most aggressive form of melanoma.
Leukemia is a blood or bone marrow cancer characterized by an abnormal increase of white blood cells. Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes in the bone marrow, which interfere with the production of normal white blood cells, red blood cells and platelets. Chronic myeloid leukemia (CML) is a cancer of the white blood cells characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood. Non-Hodgkin lymphomas can be aggressive or indolent, may occur at any age and are often marked by lymph nodes that are larger than normal, fever, and weight loss. B cell non-Hodgkin lymphomas include Burkitt lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma and mantle cell lymphoma. T cell non-Hodgkin lymphomas include mycosis fungoides, anaplastic large cell lymphoma, and precursor T-lymphoblastic lymphoma.
Renal cell carcinoma, which includes renal cell carcinoma, renal pelvis carcinoma and Wilms tumor, is the most common type of kidney cancer in adults. In 2010, there were 58,240 estimated new cases and 13,040 deaths in the United States alone.
Although significant advances through molecular biology in the identification of tumor antigens and their production in recombinant and synthetic form have allowed many sophisticated approaches in cancer treatment, the immunogenic success of tumor cell vaccines ultimately depends on major histocompatibility complex (MHC) expression on antigen-presenting cells and the recognition of tumor antigens as “foreign” by the host immune system. Prevention and treatment, however, are hampered by the ability of pathogens to escape the host immune response.
Accordingly, there is a strong need in the art for the development of new prophylactic and treatment options for viral and cancer diseases.
Nitazoxanide (2-(acetolyloxy)-N-(5-nitro-2-thiazolyl) benzamide) is a thiazolide antiparasitic agent having the following structure:

Tizoxanide is the active circulating metabolite of nitazoxanide. Following oral administration of nitazoxanide or mixtures of nitazoxanide plus tizoxanide in humans, these compounds are partially absorbed from the intestinal tract, and nitazoxanide is rapidly hydrolyzed to form tizoxanide in plasma. Tizoxanide is bound to plasma proteins and its urinary elimination half-life is 7.3 hours. Tizoxanide is glucurono-conjugated, and the drug is eliminated in urine and bile as tizoxanide or tizoxanide glucuronide. The half-life of tizoxanide in plasma is only approximately 1.5 hours. Tizoxanide has the following structure:

RM-4848 is a substituted thiazolide having the same structure as tizoxanide, but including a chloro group substituted for the nitro group, thus resulting in the compound N-(5-chlorothiazol-2-yl)-2-hydroxybenzamide. Nitazoxanide (Alinia®, NTZ) and tizoxanide (TIZ) are thiazolide compounds with activity against parasites, anaerobic bacteria, and viruses. NTZ is approved in the United States for the treatment of diarrhea caused by Cryptosporidium parvum and Giardia lamblia. NTZ and TIZ also inhibit replication of RNA and DNA viruses including influenza A and hepatitis C viruses. In clinical trials, NTZ was shown to be effective in treating rotavirus gastroenteritis, norovirus gastroenteritis and chronic hepatitis C, and is in late-stage clinical development for treatment of influenza.